The Neuropathology/Tissue Resource Core (NPTRC) provides essential neuropathology, quantitative morphometry/stereology, automated image analysis/lesion mapping and tissue banking support services to ADRC and outside investigators, projects, pilots and other Cores. NPTRC professional and technical staff is responsible for providing neuropathologic diagnoses based on NIA/AARP consensus age-adjusted quantitative criteria for Alzheimer's disease. Neuropathologic data are compared with Clinical and Psychometric Core data with the assistance of the Biostatistics Core. Brains for study will be obtained at autopsy from cognitively well characterized (WU Clinical Dementia Rating [CDR]), longitudinally studied subjects who are nondemented or who have probable DAT or related dementias. Other NPTRC services include participation in Consortium to Establish a Registry for Alzheimer's Disease (CERAD) activities, conducting weekly braincutting and microscopic diagnostic/teaching conferences dealing with AD and related dementias, providing quantitative morphometric data on AD marker lesions, including cerebral atrophy, senile plaques [SP], neurofibrillary pathology [neurofibrillary tangles (NFT), neuropil threads (NT), and neuritic senile plaques (N-SP)], and cerebral amyloid angiopathy (CAA) evaluation; neuronal stereologic analysis; and automated image analysis with large scale mapping and 3-D lesion spatial distribution (clustering) statistical analysis of SP and neurofibrillary pathology. AD-type lesions will be identified and quantified using a variety of conventional and specialized staining methods, including four silver methods, combined with immunohistochemical (IHC) marker-specific antibody probes. To complement these conventional diagnostic methods, we will also use a Core-developed sequential Gallyas silver and anti-betaA4 method to visualize the full range of SP and neurofibrillary lesions. At autopsy, fresh frozen and lightly fixed (suitable for IHC) brain tissue from defined sites and CSF samples will be obtained, stored at -85C and later distributed to ADRC and outside investigators. Antemortem blood and CSF samples will be similarly stored and distributed. These activities complement but are budgetarily and scientifically distinct from those of the Program Project, Healthy Aging and Senile Dementia (A003991).